British Pat. No. 1,360,009 discloses, inter alia, compounds of the formula (II): ##SPC3##
and their salts, esters and ethers wherein A.sub.1 is a hydrocarbon group of 1 - 20 carbon atoms and A.sub.2 is an alkyl group of 1 - 20 carbons. Such compounds are now known to possess anti-hypertensive activity of a good level. However, a detailed study has shown that the compounds disclosed in that application have a level of renal toxicity which, while not being of such a level as to necessarily rule out the use of the compounds of formula (I) as short term anti-hypertensives, is sufficiently high to suggest that the compounds of formula (I) are not suitable for long term therapy.
A considerable advance was reached with the development of the compounds specifically described in U.S. application Ser. No. 324,222, (U.S. Pat. No. 3,853,899). The preferred compounds of that application were those of the formula (III): ##SPC4##
and their salts, wherein R.sub.3 is alkyl of 4 to 10 carbon atoms and R.sub.4 is a hydrocarbon of 7 to 12 carbon atoms preferably 2-propenyl, 2-phenylethyl, benzyl, 1-naphthylmethyl or 2-naphthylmethyl. It was found that these compounds had a high level of anti-hypertensive activity coupled with low central nervous system depressant activity and improved renal toxicity.
It has now been surprisingly discovered that a particularly good level of anti-hypertensive activity coupled with a particularly low level of central nervous system depressant activity and a greatly reduced level of renal toxicity is exhibited by a particular sub-group of those compounds.
At present no explanation for the improved properties can be given but repeated tests have confirmed them.